1. Field of the Invention
The present invention relates to a method for treatment of light-injured retinal degeneration disease.
2. Related Arts
In the structure of eye, the retina exists at the ocular fundus and takes charge of the function of eye, which recognizes the presence or absence, and the shape of things in virtue of the existence of the neuroepithelial layer in the retina. In addition, the central portion of the retina is called macula lutea and one can distinguish things and feel colors by the action of the macula lutea.
The retina is destined to chronic exposure to light throughout the life. Particularly, the macula lutea, the central and most vital area of the retina, is likely to be damaged by light than the peripheral region of the retina. It has been pointed out that damage to the retina resulting from light exposure is accumulative and that the damage may promote age-related changes of retina which induce age-related macular degeneration or the like (Young, R. W.; Surv. Ophthalmol., 32: 252-269; 1988, the disclosures of which are herein incorporated by reference). It has also been described that light exposure may cause pathological conditions similar to that of age-related macular degeneration, i. e., a formation of drusen, neovascularization originated from choroidal membrane and the like. Statistically, age-related macular degeneration patients have been reported to be less likely cataract patients and more likely out-door laborers or habitants in UV-rich area.
The age-related macular degeneration is classified into the non-leakage type (dry type), which is simply called as age-related macular degeneration, and the exudative type, which is called as age-related disciform macular degeneration. In the dry type, drusen and atrophy of pigment epithelium may be observed in the macula lutea, and the vision may be damaged significantly. In the exudative type, new blood vessels originated from the choroidal membrane may develop in the macula lutea under the retina membrane, which resulting in hemorrhage, exudation and cicatrization, and further, in degeneration of the macula lutea. In the progressed stage, the visual loss becomes advanced and irreversible. At present, no effective treatment is available for the dry (non-leakage) type age-related macular degeneration. For the exudative type, it has been said that the only treatment, which might be effective, is laser photocoagulation. Recently, the effect of interferon for treatment of the exudative type was studied, but this could not necessarily be said as effective because of its side effects.
The calcium antagonists inhibit inflow of calcium ions into the vascular smooth muscle cells thereby relax the muscle to dilate the peripheral blood vessel, and thereby decrease the vascular resistance and increase the blood circulation. Clinically, they are used not only as hypotensive drugs but also as cerebral vasodilators.
In addition, in the ophthalmic field, the calcium antagonists have been attempted to use for treatment of low-tension glaucoma and it was reported that improvement of the visual field was observed in some cases. It has also been reported that the calcium antagonists increase the blood circulation in choroid, retina and optic disc (See WO97/40834, the disclosures of which are herein incorporated by reference). Based on the above actions, some calcium antagonists, for example dihydropyridine calcium antagonists such as nicardipine and pranidipine, have been concluded to be effective for treatment of ischemia-reperfusion disorder of retina (see Yasuo Hosobe, J Jpn Ophthalmol Soc 100: 665-671 (1996), and Japanese Patent Laid Open No. 10/72347, the disclosures of each of which are herein incorporated by reference).
Any efficacy of the calcium antagonists on the light-injured retinal degeneration disease, however, can not be expected from these publications. Increase in blood flow in ocular tissues such as choroid results in increase in oxygen feed to the neuroepithelial layer. It has been known, however, that light-induced retinal disorder is promoted under such condition (Jaffe, G. J. et al; Ophthalmology, 95: 1130-1141; 1988, the disclosures of which are herein incorporated by reference). It has also been described that Nimodipine, one of the dihydropyridine calcium antagonists, was not effective to light-induced retinal disorder (Li, J. et al; Research Communication in Chemical Pathology and Pharmacology, 72: 347-352; 1991, the disclosures of which are herein incorporated by reference).